The purpose of this study is to continue analyses of HIV incidence among a cohort of uninfected injection drug users (IDUs), and provide time-sensitive identification of risk factors for infection. In addition, we will study morbidity and mortality associated with injection drug use, including the natural history of hepatitis C virus (HCV) infection. To meet these aims, we will continue to prospectively follow 1000 HIV-seronegative IDUs on a semi-annual basis, among whom we have maintained a follow-up rate of 90 percent/yr and an HIV incidence greater than 2 percent/year since 1988. Over a 4 year period, we will identify temporal trends in HIV incidence and morbidity and mortality using person-time methods. We will determine period-specific HIV risk factors and attributable risks associated with illicit drug use and sexual behaviors using Poisson regression. We propose to determine the extent to which the use of a new survey method, audio computer-assisted self- interviewing (A-CASI) is associated with higher rates of self-reported HIV risk behaviors over time compared to interviewer-administered questionnaires, and the magnitude of these associations with respect to HIV seroconversion. Continuation of this cohort will enable us to evaluate the effectiveness of HIV behavioral interventions (e.g. needle exchange and pharmacy access to sterile syringes), using descriptive statistics and Poisson regression to compare users/non-users of these programs. We will examine morbidity and mortality in HIV seronegative IDUs as a basis for quantifying health effects of illicit drug use (compared to local population data), as a competing factor for HIV seroconversion (within the cohort), and as a basis for an HIV-seropositive cohort (DA04334) to identify HIV-related non-AIDS outcomes in the era of highly active antiretroviral therapy. We will characterize the natural history and pathogenesis of HCV infection including evaluation of interactions between HIV infection and HCV. The ongoing nature of this cohort allows for rapid assessment of emerging blood-borne pathogens. Eleven ongoing and already separately funded studies critically depend on this cohort to provide a key population base for their studies.